secondary hypertension work up

الرحمن ا بسمالرحيم

Secondary Hypertension Work-up

By

Tamer Moustafa Abe Elghany

MD, FESC

Overview

“ Secondary” HTN accounts for ~5-10% of other cases and represents potentially curable disease

Often overlooked and underscreened Controversy over screening and

treatment in some cases

Overview

Testing for 2ry HTN can be expensive and requires high index of clinical suspicion.

General principles: New onset HTN if <30 or >50 years of age HTN refractory to medical Rx (>3-4 meds) Specific clinical/lab features typical for dz :

Routine Laboratory Tests

1. Urinalysis

2. Complete blood count

3. Blood chemistry (potassium, sodium and creatinine)

4. Fasting glucose

5. Fasting lipid profile

6. Standard 12-leads ECG

Investigation of all patients with hypertension

Renal Parenchymal Disease

Common cause of secondary HTN (2-5%)

HTN is both cause and consequence of renal disease

Assessment of creatinine clearance and GFR are diagnostic.

Renovascular HTN

Incidence 1-30% Etiology

Atherosclerosis 75-90% Fibromuscular dysplasia 10-25% Other

Aortic/renal dissection Takayasu’s arteritis Thrombotic/cholesterol emboli CVD Post transplantation stenosis Post radiation

Renovascular HTN - Clinical History

Onset HTN age <30 or >55 Negative FH of HTN Sudden onset uncontrolled HTN in previously well controlled pt Accelerated/malignant HTN Intermittent pulm edema with nl LV fxn

Clinical exam. /Lab. findings Epigastric bruit, particulary systolic/diastolic Advanced fundal changes, grade III/IV retinopathy Azotemia induced by ACEI, ARBs or diuretics Paradoxical worsening of HTN with diuretics 2ry aldosteronism : ↑ plasma renin & ↓ s. Na&K Unilateral small kidney, difference >1.5cm, on sonography

Renovascular HTN - diagnosis

Physical findings (bruit) Duplex U/S Captopril renography Magnetic Resonance Angiography Renal Angiography

RAS screening/diagnosticsSens Spec Limitation/Etc

Duplex U/S 90-95% 60-90%Operator dependent, 10-20%

Captopril Renography 83-91% 87-93%

Accuracy reduced in pt with renal insufficiency, lacks anatomical info; good predictor of BP response

MRA 88-95% 95% False positive artifact resp, peristalsis, tortuous vessels; cost

Bruit 39-65% 90-99%Insensitive, severe stenosis may be silent

Angiography Gold std

Gold std

Invasive, nephrotoxicity, little value in predicting BP response

Screening Strategy (Index of suspicion & need intervention)

Fibromuscular dysplasia

10-25% of all RAS Young female, age 15-40 Medial disease 90%, often involves

distal RA

Atherosclerotic RAS

75-90% of RAS Usually men, age>55, other atherosclerotic dz

Fibromuscular Dysplasia, beforeand after PTRA

Atherosclerotic RAS before and after stentSafian & Textor. NEJM 344:6;

Primary Aldosteronism

Primary Aldosteronism, previously felt to be an unlikely cause of 2ry HTP, now is more commonly observed depending on the severity of HTP :

8% Stage 2 13% of Stage 3) and 20% of those with resistant hypertension.

(10th Annual SMA-ASH Carolinas Georgia Chapter Meeting, 2006)

Primary Aldosteronism

Prevalence .5- 2.0% (5-12% in referral centers) Etiology

Adrenal adenoma Bilat adrenal hyperplasia, glucocorticoid suppressible hyperaldo,

adrenal carcinoma

Clinical: May be asymptomatic. Headache, weakness, paralysis, polyuria Retinopathy, edema uncommon Hypokalemia (K normal in 40%), metabolic alkalosis, high-nl Na

Screening for Hyperaldosteronism

• Spontaneous hypokalemia (<3.5 mmol/L).

• Profound diuretic-induced hypokalemia (<3.0 mmol/L).

• Hypertension refractory to treatment with 3 or more drugs.

• Incidental adrenal adenomas.

Pheochromocytoma

Catecholamine-producing neuroendocrine tumor that arises from chromaffin cells

Adrenal Medulla : 80-85% pheochromocytomas

Extra-adrenal paragangliomas Often in head and neck (glomus jugulare) and

rarely produce catecholamines. Some can be dopamine producing.

Epidemiology

Incidence: 1 in 100,000 each year Prevalence among pts with HTP

In adults – 0.1-0.6% In children – 1%

Traditional rule of 10 10% bilateral, 10% familial, 10% extra-adrenal, and

10% malignant.Recent reports found 12-24% of sporadic

pheochromocytoma with germline mutation.

Clinical Presentation

Paroxysmal attacks of Headache, palpitations, and sweating.

Adults more often have paroxysmal hypertension (50%) while

Children have sustained hypertension (70-90%) 20% of children will be normotensive at diagnosis.

Screening for Pheochromocytoma

• Paroxysmal and/or severe sustained hypertension refractory to usual antihypertensive therapy;

• Hypertension and symptoms suggestive of catecholamine excess (two or more of headaches, palpitations, sweating, etc);

• Hypertension triggered by B-blockers, MAO inhibitors, clonidine, micturition, changes in abdominal pressure or tyramine containing foods.

• Incidentally discovered adrenal mass.

• Multiple endocrine neoplasia (MEN) 2A (medullary carcinomas of thyroid) or 2B (mucosal neuromas) ; von Recklinghausen’s neurofibromatosis, or von Hippel-Lindau disease.

Pheochromocytoma – Screening. Best detected during or immediately after

episodes

Sensitivity Specificity

Plasma free metanephrine >.66nmol/L

99% 89%

24hr urine metanephrine(>3.7nmol/d)

77% (95%) 93% (96%)

24 urine VMA 64% 95%

Lenders, et al. JAMA 2002 Mar 20;287(11):1427-34

Pheochromocytoma - Diagnosis

Imaging for localization of tumor

Sens Spec PPV NPV

(MIBG) scintigraphy 78% 100% 100% 87%

CT 98% 70% 69% 98%

MRI 100% 67% 83% 100%

Akpunonu, et al. Dis Month.October 1996, p688

Cushing’s syndrome/ hypercortisolism

Rare cause of secondary HTN (.1-.6%) Etiology: pituitary microadenoma, iatrogenic (steroid use), ectopic ACTH, adrenal adenoma Clinical

Sudden weight gain, truncal obesity, moon facies, abdominal striae, DM/glucose intolerance, HTN, prox muscle weakness, skin atrophy, hirsutism/acne

Cushings syndrome

Cushings syndrome - diagnosis

Screen: 24 Hr Urine free cortisol >90ug/day is 100% sens and 98% spec false + in Polycystic Ovarian Syndrome, depression

Confirm Low dose dexamethasone suppression test 1mg dexameth. midnight, measure am plasma cortisol

(>100nmol is +) Other tests include dexa/CRH suppresion test

Imaging CT/MRI head (pit) chest (ectopic ACTH tumor)

Coarctation of Aorta Congenital defect, male>female

Clinical Differential systolic BP arms vs legs

(=DBP) May have differential BP in arms if defect

is prox to L subclavian art Diminished/absent femoral art pulse Often asymptomatic Echo-Doppler, CT angiography,

aortography.

Coarctation of Aorta

Brickner, et al. NEJM 2000;342:256-263

Hyperthyroidism

33% of thyrotoxic pt develop HTN Usually obvious signs of thyrotoxicosis Dx: TSH, Free T4/3, thyroid RAIU

Hypothyroidism

25% hypothyroid pt develop HTN Mechanism mediated by local control, as

basal metabolism falls so does accumulation of local metabolites; relative vasoconstriction ensues

Summary

Screening for 2ry HTN can be expensive and requires clinical suspicion and knowledge of limitations of different tests

General principles: New onset HTN if <30 or >50 years of age HTN refractory to medical Rx (>3-4 meds) Specific clinical/lab features typical for dz :

@ Hypokalemia in the absence of diuretic therapy may indicate a state of mineralocorticoid excess

@ Excess aldosterone production (Conn’s)

@Excess glucocorticoid production (Cushing’s)

@Excess T3&T4 (hyperthyroidism)

@ Epigastric bruits, differential BP in arms, episodic HTN/flushing/palp.

Summary

Tamer MD, FESC